The Experts below are selected from a list of 125088 Experts worldwide ranked by ideXlab platform
Joseph K Balciunas - One of the best experts on this subject based on the ideXlab platform.
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the role of pre release Efficacy Assessment in selecting classical biological control agents for weeds applying the anna karenina principle
Biological Control, 2005Co-Authors: A S Mcclay, Joseph K BalciunasAbstract:The goals in selecting classical biological control agents for weeds are to identify agents that will be both safe for release and effective in controlling their target plants. The release of ineffective agents should be avoided, as these add to the costs and risks of biological control without contributing to its benefits. While the principles of host-specificity testing and risk Assessment for weed biological control agents have been extensively debated and refined, there has been less attention given to assessing the probable Efficacy of agents prior to release. This reluctance to undertake pre-release Efficacy Assessment (PREA) is probably based on concerns that it will both add to the cost of screening biological control agents and introduce a risk of wrongly rejecting effective agents. We used a project simulation model to investigate the implications of using PREA as an additional filter in the agent selection process. The results suggest that, if it can be done at a lower cost than host-specificity testing, the use of PREA as the first filter can make agent selection more cost-effective than screening based on host-specificity alone. We discuss examples of PREA and potential approaches. The impact of biocontrol agents is a function of their range, abundance, and per-capita damage. While it will always be difficult to predict the post-release abundance of biological control agents from pre-release studies, some estimates of potential range can be obtained from studies of climatic adaptation. For agents that affect the vegetative growth or survival of their target weeds, experimental measurement of per-capita damage is feasible and can contribute to a reduction in the numbers of ineffective agents released. The Anna Karenina principle states that success in complex undertakings does not depend on a single factor but requires avoiding many separate causes of failure. We suggest that, in biological control of weeds, the use of agents that are not sufficiently damaging is one such cause that can be partially avoided by the use of pre-release Efficacy Assessment.
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The role of pre-release Efficacy Assessment in selecting classical biological control agents for weeds—applying the Anna Karenina principle
Biological Control, 2005Co-Authors: A S Mcclay, Joseph K BalciunasAbstract:The goals in selecting classical biological control agents for weeds are to identify agents that will be both safe for release and effective in controlling their target plants. The release of ineffective agents should be avoided, as these add to the costs and risks of biological control without contributing to its benefits. While the principles of host-specificity testing and risk Assessment for weed biological control agents have been extensively debated and refined, there has been less attention given to assessing the probable Efficacy of agents prior to release. This reluctance to undertake pre-release Efficacy Assessment (PREA) is probably based on concerns that it will both add to the cost of screening biological control agents and introduce a risk of wrongly rejecting effective agents. We used a project simulation model to investigate the implications of using PREA as an additional filter in the agent selection process. The results suggest that, if it can be done at a lower cost than host-specificity testing, the use of PREA as the first filter can make agent selection more cost-effective than screening based on host-specificity alone. We discuss examples of PREA and potential approaches. The impact of biocontrol agents is a function of their range, abundance, and per-capita damage. While it will always be difficult to predict the post-release abundance of biological control agents from pre-release studies, some estimates of potential range can be obtained from studies of climatic adaptation. For agents that affect the vegetative growth or survival of their target weeds, experimental measurement of per-capita damage is feasible and can contribute to a reduction in the numbers of ineffective agents released. The Anna Karenina principle states that success in complex undertakings does not depend on a single factor but requires avoiding many separate causes of failure. We suggest that, in biological control of weeds, the use of agents that are not sufficiently damaging is one such cause that can be partially avoided by the use of pre-release Efficacy Assessment.
A S Mcclay - One of the best experts on this subject based on the ideXlab platform.
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the role of pre release Efficacy Assessment in selecting classical biological control agents for weeds applying the anna karenina principle
Biological Control, 2005Co-Authors: A S Mcclay, Joseph K BalciunasAbstract:The goals in selecting classical biological control agents for weeds are to identify agents that will be both safe for release and effective in controlling their target plants. The release of ineffective agents should be avoided, as these add to the costs and risks of biological control without contributing to its benefits. While the principles of host-specificity testing and risk Assessment for weed biological control agents have been extensively debated and refined, there has been less attention given to assessing the probable Efficacy of agents prior to release. This reluctance to undertake pre-release Efficacy Assessment (PREA) is probably based on concerns that it will both add to the cost of screening biological control agents and introduce a risk of wrongly rejecting effective agents. We used a project simulation model to investigate the implications of using PREA as an additional filter in the agent selection process. The results suggest that, if it can be done at a lower cost than host-specificity testing, the use of PREA as the first filter can make agent selection more cost-effective than screening based on host-specificity alone. We discuss examples of PREA and potential approaches. The impact of biocontrol agents is a function of their range, abundance, and per-capita damage. While it will always be difficult to predict the post-release abundance of biological control agents from pre-release studies, some estimates of potential range can be obtained from studies of climatic adaptation. For agents that affect the vegetative growth or survival of their target weeds, experimental measurement of per-capita damage is feasible and can contribute to a reduction in the numbers of ineffective agents released. The Anna Karenina principle states that success in complex undertakings does not depend on a single factor but requires avoiding many separate causes of failure. We suggest that, in biological control of weeds, the use of agents that are not sufficiently damaging is one such cause that can be partially avoided by the use of pre-release Efficacy Assessment.
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The role of pre-release Efficacy Assessment in selecting classical biological control agents for weeds—applying the Anna Karenina principle
Biological Control, 2005Co-Authors: A S Mcclay, Joseph K BalciunasAbstract:The goals in selecting classical biological control agents for weeds are to identify agents that will be both safe for release and effective in controlling their target plants. The release of ineffective agents should be avoided, as these add to the costs and risks of biological control without contributing to its benefits. While the principles of host-specificity testing and risk Assessment for weed biological control agents have been extensively debated and refined, there has been less attention given to assessing the probable Efficacy of agents prior to release. This reluctance to undertake pre-release Efficacy Assessment (PREA) is probably based on concerns that it will both add to the cost of screening biological control agents and introduce a risk of wrongly rejecting effective agents. We used a project simulation model to investigate the implications of using PREA as an additional filter in the agent selection process. The results suggest that, if it can be done at a lower cost than host-specificity testing, the use of PREA as the first filter can make agent selection more cost-effective than screening based on host-specificity alone. We discuss examples of PREA and potential approaches. The impact of biocontrol agents is a function of their range, abundance, and per-capita damage. While it will always be difficult to predict the post-release abundance of biological control agents from pre-release studies, some estimates of potential range can be obtained from studies of climatic adaptation. For agents that affect the vegetative growth or survival of their target weeds, experimental measurement of per-capita damage is feasible and can contribute to a reduction in the numbers of ineffective agents released. The Anna Karenina principle states that success in complex undertakings does not depend on a single factor but requires avoiding many separate causes of failure. We suggest that, in biological control of weeds, the use of agents that are not sufficiently damaging is one such cause that can be partially avoided by the use of pre-release Efficacy Assessment.
Horacio Rey - One of the best experts on this subject based on the ideXlab platform.
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comparative Efficacy Assessment of tamsulosin vs tamsulosin plus tadalafil in the treatment of luts bph pilot study
The Journal of Sexual Medicine, 2008Co-Authors: Amado Bechara, Salomón Víctor Romano, A. Casabe, Sergio Haime, Pablo Dedola, Cecilia Hernández, Horacio ReyAbstract:ABSTRACT Introduction The high incidence of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in aging men and the same pathophysiology make probable to treat both disorders with the same treatment. Numerous authors evaluated the actions of PDE5i in improving the LUTS/(benign prostate hyperplasia) BPH. Aim To assess the Efficacy and safety of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day in patients with LUTS in a crossover design study. Main Outcomes Measures International Prostate Symptoms Score (IPSS), IPSS Quality of Life (IPSS‐QOL), maximum flow rate (Qmax), post‐void residual volume (PVR), International Index of Erectile Function‐Erectile Function Domain (IIEF‐EF), Global Assessment Quality (GAQ). For the statistical analysis, a Tukey‐Kramer multicomparison test was used. Methods A randomized, double‐blind, crossover study was conducted from September 2007 to February 2008 in one center. Thirty men, older than 50 years old, with a history of LUTS/BPH of at least 6 months, were randomized into two groups to receive tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day for 45 days, and then switched to the other treatment mode for other 45 days. Results Twenty‐seven patients completed the study. Improvements of IPSS score and IPSS‐QOL were significant with both treatments but greater with the drug combination. Both regimens similarly improved the Qmax and decreased the PVR volume from baseline ( P P > 0.05). The IIEF improved with tamsulosin plus tadalafil ( P P > 0.05). The GAQ showed that all patients preferred the combination scheme. Both treatments were well tolerated. Conclusion Tamsulosin 0.4 mg/day plus tadalafil 20 mg/day was more effective than tamsulosin 0.4 mg/day alone to improve LUTS and erectile dysfunction and was also well tolerated. Large‐scale, randomized, placebo‐controlled studies are needed to further assess the long‐term safety and effectiveness of these agents in treating LUTS/BPH with or without ED. Bechara A, Romano S, Casabe A, Haime S, Dedola P, Hernandez C, and Rey H. Comparative Efficacy Assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study. J Sex Med 2008;5:2170–2178.
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Comparative Efficacy Assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study.
The journal of sexual medicine, 2008Co-Authors: Amado Bechara, Salomón Víctor Romano, A. Casabe, Sergio Haime, Pablo Dedola, Cecilia Hernández, Horacio ReyAbstract:ABSTRACT Introduction The high incidence of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in aging men and the same pathophysiology make probable to treat both disorders with the same treatment. Numerous authors evaluated the actions of PDE5i in improving the LUTS/(benign prostate hyperplasia) BPH. Aim To assess the Efficacy and safety of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day in patients with LUTS in a crossover design study. Main Outcomes Measures International Prostate Symptoms Score (IPSS), IPSS Quality of Life (IPSS‐QOL), maximum flow rate (Qmax), post‐void residual volume (PVR), International Index of Erectile Function‐Erectile Function Domain (IIEF‐EF), Global Assessment Quality (GAQ). For the statistical analysis, a Tukey‐Kramer multicomparison test was used. Methods A randomized, double‐blind, crossover study was conducted from September 2007 to February 2008 in one center. Thirty men, older than 50 years old, with a history of LUTS/BPH of at least 6 months, were randomized into two groups to receive tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day for 45 days, and then switched to the other treatment mode for other 45 days. Results Twenty‐seven patients completed the study. Improvements of IPSS score and IPSS‐QOL were significant with both treatments but greater with the drug combination. Both regimens similarly improved the Qmax and decreased the PVR volume from baseline ( P P > 0.05). The IIEF improved with tamsulosin plus tadalafil ( P P > 0.05). The GAQ showed that all patients preferred the combination scheme. Both treatments were well tolerated. Conclusion Tamsulosin 0.4 mg/day plus tadalafil 20 mg/day was more effective than tamsulosin 0.4 mg/day alone to improve LUTS and erectile dysfunction and was also well tolerated. Large‐scale, randomized, placebo‐controlled studies are needed to further assess the long‐term safety and effectiveness of these agents in treating LUTS/BPH with or without ED. Bechara A, Romano S, Casabe A, Haime S, Dedola P, Hernandez C, and Rey H. Comparative Efficacy Assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study. J Sex Med 2008;5:2170–2178.
Davy Xuesong Ouyang - One of the best experts on this subject based on the ideXlab platform.
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Abstract 2167: Efficacy Assessment of BTK inhibitor ibrutinib in de novo and viral-induced B cell lymphoma
Tumor Biology, 2018Co-Authors: Jessie Wang, Xuesong Huang, Meiling Zheng, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Davy Xuesong OuyangAbstract:Bruton9s tyrosine kinase (BTK) is crucial for B cell maturation. Its activation has also been considered as a major oncogenic driver for various B cell-derived lymphoid cancers. A BTK inhibitor, Ibrutinib, has been approved for mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenstrom9s macroglobulinemia, a form of non-Hodgkin9s lymphoma (NHL). Ibrutinib has also shown encouraging efficacies in defuse large B cell lymphoma (DLBCL), specifically in activated B cell-like (ABC) subtype, but not in germinal center B cell-like (GCB) subtype. We have established a series of patient derived xenograft (PDX) models, recapitulating diverse genotypes of de novo DLBCL patients, including two MYD88L265P/CD79BY197N double mutants (LY2298, LY2264), one MYD88L265P single mutant (LY0257), and a variety of wild-types (LY2214, LY3604, and LY6934, etc.). This cohort of PDX models serve as perfect preclinical tools to investigate Ibrutinib responses in different genotypes. Our studies demonstrated a moderate to robust efficacies of Ibrutinib in the MYD88/CD79B double mutants, suggesting that CD79B mutation is the predictive biomarker for chronic activation of B cell receptor (BCR) signaling, as well as generally good responses to BTK inhibitor. Interestingly, the MYD88 single mutant model LY0257, where the disease is likely driven by constitutive activation of MYD88 signaling, also showed response to Ibrutinib when dosed in drinking water. In the wild type PDXs, two of seven models tested so far are either partially responsive or sensitive to Ibrutinib, while the others are resistant to the treatment. It seems that Ibrutinib response does not always require CD79B mutation, and BCR pathway addiction may occur by other means in DLBCL, even when MYD88 signaling is constitutively active. Notably, all 5 wild type DLBCL PDXs that are non-responsive to Ibrutinib are EBV positive verified by RNAseq. These EBV-transformed B lymphoma PDX models, which share the similar histopathology as de novo DLBCL, but have distinct molecular pathology signatures and different pathogenesis. In Efficacy studies, none of the transformed B lymphoma PDXs showed response to Ibrutinib. Taken together, our DLBCL and EBV-induced lymphoma PDX models provide a valuable preclinical platform for evaluating BTK inhibitors, as well as future drug discovery efforts on other targets in the BCR and MYD88 pathways, such as PI3K, SYK, and IRAK4. Citation Format: Jessie Jingjing Wang, Meiling Zheng, Xuesong Huang, Yanrui Song, Wubin Qian, Likun Zhang, Jie Cai, Sheng Guo, Henry Qixiang Li, Davy Xuesong Ouyang. Efficacy Assessment of BTK inhibitor ibrutinib in de novo and viral-induced B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2167.
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Abstract A203: Generation of human TIM3 knock-in mice for preclinical Efficacy Assessment of therapeutic antibodies
Immune Checkpoints, 2018Co-Authors: Lei Zheng, Gang Chen, Jean-pierre Wery, Jay Liu, Xin Dong, Xuesong Huang, Wenyi Ouyang, Qian Shi, Davy Xuesong OuyangAbstract:Immune checkpoint inhibitors, i.e., PD1 and CTLA4 antibody therapeutics, have led to long-term survival in many late-stage solid tumor patients. Despite this revolutionary clinical impact, the overall response rate is still low. One major roadblock is that compensatory immune inhibitory pathways were turned on to protect tumor cells from being attacked by T cells. T cell immunoglobulin- and mucin domain-containing molecule 3 (Tim-3) is a type I transmembrane protein expressed in T cells, monocytes, macrophages, and dendritic cells. PD-1 and Tim-3 coexpression is often associated with an exhausted phenotype of tumor-infiltrating lymphocyte (TIL) in various tumor types. TIM-3 expression has been reported as a compensatory mechanism in the PD1 nonresponsive patients. Simultaneously targeting PD1 and TIM3 is now being actively tested in clinical trials. However, we still do not have an animal model that can efficiently evaluate the Efficacy of therapeutic TIM3 antibodies or combinations. Here we report generation of a human TIM3 knock-in C57BL/6 mouse model, in which we replaced mouse exon 2-5 of HAVCR2 gene with human counterparts. The engineered knock-in mice express a chimeric TIM3 where its extracellular and transmembrane domains are human sequence, while the signal peptide and intracellular domain are kept intact. We confirmed that homozygous knock-in mice only express this chimeric TIM3, recognizable by human TIM3 antibody in NK cells, macrophages, and stimulated T cells. In an Efficacy study, we inoculated the TIM3 knock-in mice with MC38 syngeneic tumor cells. Treating the mice with 5 mg/kg of human TIM3 antibody resulted in modest tumor growth inhibition (TGI), while in combination with anti-mouse PD1 antibody, the TGI improved to 62% following 2 weeks of treatment. We are now breeding the human PD1 and human TIM3 double knock-in mice to test the combinatory therapeutic antibodies. We have also developed human PD-L1 expressing MC38 cells, so that when inoculated in human TIM3 knock-in mice, PD-L1 and TIM3 therapeutic combination can be evaluated. Citation Format: Lei Zheng, Xuesong Huang, Wenyi Ouyang, Gang Chen, Annie Xiaoyu An, Xin Dong, Jay Liu, Jean Pierre Wery, Qian Shi, Davy Xuesong Ouyang. Generation of human TIM3 knock-in mice for preclinical Efficacy Assessment of therapeutic antibodies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A203.
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Abstract 1658: Establishment of CD137 humanized mouse model for Efficacy Assessment of agonistic anti-CD137 therapeutic antibodies
Immunology, 2017Co-Authors: Davy Xuesong Ouyang, Gang Chen, Zhensheng Wang, Lei Zheng, Jean-pierre Wery, Jay Liu, Xin DongAbstract:CD137 belongs to the TNF receptor super family, and its activation is essential to the function of T cells and NK cells. Multiple agonistic CD137 antibodies are currently being tested in humans with advanced cancer, which expected to become an important new immuno-oncology therapeutics in clinic. It is important to establish preclinical models for Efficacy Assessment of investigational CD137 antibodies before entering clinic. Currently available animal models cannot meet this need. Syngeneic mouse tumor models provide a useful platform for testing surrogate immuno-oncology therapies, but cannot be used for testing human therapeutic antibodies due to the species specificity; human immunity reconstituted models, by human PBMC or hematopoietic stem cell inoculation into immune deficient mice, suffering from highly variable responses, are not robust enough to provide a reliable system for Efficacy studies. Establishing target humanized models by replacing mouse therapeutic target with human counterpart while maintaining normal mouse immunity is a practical approach to evaluate human therapeutic antibodies in vivo. Using CRISPR-Cas9 gene editing, we have engineered human CD137 knock-in model expressing chimeric human/mouse CD137 composed of human extracellular and transmembrane domains (Exon 4-7), with intact mouse signal peptide and intracellular domain. FACS analysis of splenocytes derived from homozygous knock-in mice showed that CD3/CD28 stimulated T cells only express chimeric CD137 reactive to human CD137 antibodies, but not mouse CD137; Yet the expression levels of the chimeric CD137 in the knock-in mice are generally lower than endogenous mouse protein in wild-type C57BL/6 mice. At present, we are testing the Efficacy of reference human CD137 agonistic antibodies by treating these homozygous knock-in mice grafted with syngeneic MC38 tumor cells. Data will be presented at the conference. Citation Format: Davy Xuesong Ouyang, Gang Chen, Zhensheng Wang, Lei Zheng, Annie Xiaoyu An, Jean-Pierre Wery, Jay Liu, Xin Dong, Henry Q. X. Li. Establishment of CD137 humanized mouse model for Efficacy Assessment of agonistic anti-CD137 therapeutic antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1658. doi:10.1158/1538-7445.AM2017-1658
Hajime Mori - One of the best experts on this subject based on the ideXlab platform.
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Process development for quantitation and vaccine Efficacy Assessment of recombinant hemagglutinin-neuraminidase
Process Biochemistry, 2020Co-Authors: Ping Ying Lye, Suriani Mohd Noor, Syamsiah Aini Shohaimi, Niny Fariza Junoh, Soo Choon Tan, Shin-ichi Iwamoto, Eiji Kotani, Mohd Nor Norazmi, Toshihiro Nagamine, Hajime MoriAbstract:Abstract Recombinant hemagglutinin-neuraminidase (HN) based subunit vaccine, which is non-infectious and can be produced using insect cell-culture systems, is a potential alternative to conventional live and inactivated Newcastle disease virus (NDV) vaccines. However, process development for manufacture and Efficacy Assessment of HN subunit vaccines has been hampered by the absence of reference standards, a cornerstone for robust and sensitive quantitative analytical methods. In this work, a downstream purification strategy was developed to obtain NDV HN which was expressed with a hexa-histidine fusion tag (rHN) to facilitate detection using generic antibodies. Highly purified rHN (∼95%) attained after detergent extraction and two-stage ion-exchange-hydroxyapatite column chromatography was subsequently utilized as reference standards for quantitative ELISA development. Recovery of rHN at different stages of purification was monitored. Quantitation of rHN from crude cell lysates was performed for dose-ranging antibody response and protective Efficacy studies. A higher dose (1500 ng) of rHN was correlated to a significant reduction in virus shedding and attainment of herd immunity, as indicated by a higher proportion of chickens (92%) with hemagglutination inhibition (HI) antibody titers ≥ log23. The outcome of this study, shows the importance of downstream process development in enabling robust quantitation and Efficacy Assessment of a recombinant subunit vaccine.
